Stem Cell-Based Cartilage Regeneration Could Decrease Knee and Hip Replacements


Work by Chul-Won Ha, director of the Stem Cell and Regenerative Medicine Institute at Samsung Medical Center and his colleagues illustrates the how stem cell treatments might help regrow cartilage in patients with osteoarthritis or have suffered from severe hip or knee injuries.

A 2011 report from the American Academy of Orthopedic Surgeons showed that approximately one million patients in the US alone (645,000 hips and 300,000 knees) have had joint replacements in the U.S. alone. Most joint replacements occur with few complications, artificial joints can only last for a certain period of time and some will even eventually require replacement. Also these procedures require extensive rehabilitation and are, in general, quite painful. A goal for regenerative medicine is the regenerate the cartilage that was worn away to prevent bones from eroding each other and obviate the need for artificial joint replacement procedures.

Extensive research from the past two decades from a whole host of laboratories in the United States, Europe, and Japan have shown that mesenchymal stem cells (MSCs) have the ability to make cartilage, and might even have the capability to regenerate cartilage in the joint of a living organism. MSCs have the added benefit of suppressing inflammation, which is a major contributor to the pathology of osteoporosis. Additionally, MSCs are also relatively easy to isolate from tissues and store.

“Over the past several years, we have been investigating the regeneration potential of human umbilical cord blood- derived MSCs in a hyaluronic acid (HA) hydrogel composite. This has shown remarkable results for cartilage regeneration in rat and rabbit models. In this latest study we wanted to evaluate how this same cell/HA mixture would perform in larger animals,” said Ha.

Ha collaborated with researchers from Ajou University, which is also in Seoul, and Jeju University in Jeju, Korea. Ha and his team used pigs as their model system, which is a better system than rodents for such research.

The stem cells for this project were isolated from human umbilical cord blood that was obtained from a cord blood bank. They isolated MSCs from the umbilical cord blood and grew them in culture to establish three different human Umbilical Cord Blood MSC lines. Then they pelleted the cells and mixed them with the HA solution and applied them to the damaged knee joints of pigs.

“After 12 weeks, there was no evidence of abnormal findings suggesting rejection or infection in any of the six treated pigs. The surface of the defect site in the transplanted knees was relatively smooth and had similar coloration and microscopic findings as the surrounding normal cartilage, compared to the knees of a control group of animals that received no cells. The borderline of the defect was less distinct, too,” said the study’s lead investigator, Yong-Beom Park, who is a colleague of Ha’s at the SungKyunKwan University’s Stem Cell and Regenerative Medicine Institute.

“This led us to conclude that the transplantation of hUCB-MSCs and 4 percent HA hydrogel shows superior cartilage regeneration, regardless of the species. These consistent results in animals may be a stepping stone to a human clinical trial in the future,” Dr. Ha noted.

“These cells are easy to obtain, can be stored in advance and the number of potential donors is high,” said Anthony Atala, M.D., Editor of STEM CELLS Translational Medicine and Director of the Wake Forest Institute for Regenerative Medicine. “The positive results in multiple species, including the first study of this treatment in large animals, are certainly promising for the many patients requiring treatments for worn and damaged cartilage.”

New Bone Marrow-Based Stem Cell Identified in Mice that Regenerates Bones and Cartilage in Adults


Researchers at Columbia University Medical Center (CUMC) have discovered a bone marrow-based stem cell capable of regenerating both bone and cartilage in mice. The discovery appeared in the online issue of the journal Cell.

These cells have been called osteochondroreticular (OCR) stem cells, and they were identified in experiments that tracked a protein expressed by these cells. By using this specific protein as a marker for OCR stem cells, the Columbia team found that OCR cells self-renew and produce key bone and cartilage cells, including osteoblasts and chondrocytes. Furthermore, when OCR stem cells are transplanted to a fracture site, they dutifully contribute to bone repair.

“We are now trying to figure out whether we can persuade these cells to specifically regenerate after injury. If you make a fracture in the mouse, these cells will come alive again, generate both bone and cartilage in the mouse—and repair the fracture. The question is, could this happen in humans,” says Siddhartha Mukherjee, MD, PhD, assistant professor of medicine at CUMC and a senior author of the study.

Since mice and humans have similar bone biology, Mukherjee and his colleagues are quite confident that OCR stem cells exist in human bone marrow. Further studies could uncover new and effective ways to exploit OCR cells to provide greater ways to prevent and treat osteoporosis, osteoarthritis, or bone fractures.

“Our findings raise the possibility that drugs or other therapies can be developed to stimulate the production of OCR stem cells and improve the body’s ability to repair bone injury—a process that declines significantly in old age,” says Timothy C. Wang, MD, the Dorothy L. and Daniel H. Silberberg Professor of Medicine at CUMC, who initiated this research. Wang and his team previously found an analogous stem cell in the intestinal tract and observed that it was also abundant in the bone.

“These cells are particularly active during development, but they also increase in number in adulthood after bone injury,” says Gerard Karsenty, MD, PhD, the Paul A. Marks Professor of Genetics and Development, chair of the Department of Genetics & Development, and a member of the research team.

Mukherjee and his coworkers also showed that adult OCR stem cells are distinct from mesenchymal stem cells (MSCs). MSCs play essential roles in bone generation during development and adulthood. Therefore, researchers thought that MSCs gave rise to all bone, cartilage, and fat, but recent studies have shown that MSCs do not generate young bone and cartilage. This study by Mukherjee and his colleagues suggests that OCR stem cells actually make young bone and cartilage, but both OCR stems cells and MSCs contribute to bone maintenance and repair in adults.

Mukherjee also suspects that OCR cells may play a role in soft tissue cancers.

A research team from Stanford University School of Medicine just released a similar study that used a different methodology to identify the same stem cell type.

Human Infra-patellar Fat Pad-Derived Stromal Cells Show Great Cartilage-Making Potential, Which is Enhanced By Connective Tissue Components


With age and overuse, our knees wear out and we sometimes need an artificial one. The cartilage shock absorber at the ends of our bones simply does not regenerate very well, and this results in large problems when we get older.

Is there an effective way to regenerate cartilage? Stem cells do have the ability to make cartilage, but finding the right stem cell and delivering enough of them to make a difference remains a challenge.

To that end, Tang-Yuan Chu and his colleagues from Tzu Chi University and the Buddhist Tzu Chi General Hospital in Hualien, Taiwan have discovered that stem cells from the fat pad that surrounds the knee appear to be one of the best sources of cartilage-making cells for the knee.

The infra-patellar fat pad or IFP contains a stem cell population called infra-patellar fat pad-derived stromal cells or IFPSCs. These IFPSCs were isolated by Chu and his colleagues from patients who were undergoing arthroscopic surgery. When Chu and others grew these cells in culture, the IFPSCs grew robustly for two weeks. The culture protocol was a standard one and no special requirements were required. In fact, after two weeks, the IFPSCs grew to more than 10 million cells on the third passage.

When the ability of IFPSCs to form cartilage-making cells (chondrocytes) were compared with mesenchymal stem cells from bone marrow, fat and umbilical cord connective tissue (Wharton’s jelly), the IFPSCs showed a clear superiority to these other cells types, and differentiated into chondrocytes quite effectively.

Next, Chu and his crew cultured the IFPSCs on a material called hyaluronic acid (HA). HA is a common component of the synovial fluid that helps lubricate our larger joints and in connective tissue, and basement membranes upon which epithelial cells sit.

Hyaluronic Acid

When grown on 25% HA, the IFPSCs were better at making bone or fat than IFPSCs grown on no HA. Furthermore, when grown on 25% HA, IFPSCs showed a four-fold increase in their ability to form chondrocytes. The HA also did not affect the ability of the cells to divide.

In conclusions, these IFPSCs seem to possess a strong potential to differentiate into chondrocytes and regenerate cartilage. Also, this ability is augmented in a growth environment of 25% HA. Certainly some preclinical trials with laboratory animal are due. Wouldn’t you say?

Source: Dah-Ching Ding; Kun-Chi Wu; Hsiang-Lan Chou; Wei-Ting Hung; Hwan-Wun Liu; Tang-Yuan Chu. Human infra-patellar fat pad-derived stromal cells have more potent differentiation capacity than other mesenchymal cells and can be enhanced by hyaluronan.  Cell Transplantation, http://dx.doi.org/10.3727/096368914X681937.

Glucosamine, Chondroitin and Delaying Osteoarthritis


I have a confession to make. I have been taking 1200 mgs of glucosamine sulfate for the past 5-6 years for my knee cartilage. I do not presently have osteoarthritis, but I am trying to stave it off by taking this supplement.

Does this supplement work? That’s hard to say for certain because the studies disagree. There are theoretical reasons to suspect that glucosamine would help with cartilage deposition. Cartilage is very rich in a group of sticky, sugary compounds called “glycosaminoglycans,” which have the unfortunate acronym of GAGs. GAGs consist of repeating two-sugar motifs, and the building block for the vast majority of these two-sugar motifs is glucosamine. Therefore, glucosamine is a main building block of a prominent component of cartilage.

What about chrondroitin? Chondroitin is a GAG that usually comes attached to a protein. This complex of GAG + backbone protein is called a “proteoglycan.” The chondroitin you get in the store is a repeating polymer of a two-sugar motif, and this complex molecule is either degraded in your digestive system by bacteria, or by our own gastrointestinal tract.  The degradation and absorption of chondroitin probably varies considerably from person to person.  If chondroitin is absorbed then the building blocks of chondroitin can potentially help build cartilage, since chondroitin-containing proteoglycans are important structural components of cartilage.  There is also the possibility that chondroitin precursors prevent the breakdown of cartilage.

Chondroitin_sulfate-over

In 2006, a good-sized study called the GAIT study was published in the New England Journal of Medicine (Clegg, D.O. et al. (2006). Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. New Eng. J. Med. 354(8):795-808). In this study, 1583 patients with symptomatic knee osteoarthritis were randomly assigned to different treatment subgroups. These groups were:

a) chondroitin sulphate alone (400 mg 3x a day)
b) glucosamine hydrochloride alone (500 mg 3x a day)
c) combined glucosamine hydrochloride/chondroitin sulphate (same doses but combined)
d) celecoxib (Celebrex®) (200 mg per day)
e) placebo (inactive dummy tablet)

Daily dosages for glucosamine and chondroitin were 1500 mgs and 1200 mgs, respectively. The efficacious dosage for these supplements have yet to be determined. Therefore, these dosages are a best guess. Celecoxib was included as a positive control for the GAIT study, since celecoxib is FDA approved for the management of osteoarthritis pain. Therefore, investigators therefore expected participants in this group to experience some pain relief, which would serve to validate the results of the GAIT study.

The GAIT study found that when patients were divided into two groups based on pain levels, 1,229 had mild pain and 354 had moderate to severe pain. With regard to the effectiveness of these supplements, neither glucosamine nor chondroitin sulphate either on their own or in combination were effective in reducing pain. However, when only those patients with moderate to severe pain was analyzed the combination of glucosamine and chondroitin sulphate was effective for pain relief. Unfortunately, no cartilage thickness studies were performed to determine if the supplements augment cartilage thickness. The GAIT study was publicly funded, and therefore, accusations of conflict of interest could not be used to discredit this study.

in 2005, results from the GUIDE study were presented at the 2005 Annual Meeting of the American College of Rheumatology. This study was funded by glucosamine manufacturers and examined of pain and mobility in 318 osteoarthritis sufferers between the ages of 45 and 75 at 13 European hospitals. Participants in this study were divided into three groups:

a) glucosamine sulphate in soluble powder form 1500mg daily
b) acetaminophen (e.g. Tylenol® and paracetamol) 3000mg daily
c) placebo

In addition, subjects in all three groups were allowed to take ibuprofen as needed as a ‘rescue’ for pain relief.

The GUIDE study found that glucosamine sulphate and acetaminophen were more effective in reducing pain than placebo. Patients who took glucosamine sulphate experienced greater pain relief than patients on acetaminophen.

The GUIDE and GAIT studies were positive for glucosamine and chondroitin, but there are negative studies too. In October 2004, Jolanda Cibere and others published a study in the journal Arthritis Care and Research in which they gave glucosamine or a placebo to arthritis suffers and then discontinued them. 42% of the patients receiving the placebo experienced a disease flare-up and 45% of the glucosamine-receiving patients experienced a flare-up. Also, the time to disease flare was not significantly different in the glucosamine compared with placebo group. Thus Cibere and others concluded that “this study provides no evidence of symptomatic benefit from continued use of glucosamine sulfate.”

The bottom line on all this is the glucosamine and chondroitin perform inconsistently in controlled studies. When poor-quality studies are excluded, glucosamine seems to delay arthritis. The highly respected Cochrane Library published a summary of human clinical trials with glucosamine and when the poor-quality trials were excluded, Towheed and his colleagues concluded that glucosamine provided relief of the symptoms of arthritis and also, based on X-rays, helped delay the onset of osteoarthritis.

However, the European Food Safety Authority reviewed over 60 articles on glucosamine and came to a completely different conclusion. In 2012, the EFSA concluded that “The Panel concludes that a cause and effect relationship has not been established between the consumption of glucosamine and maintenance of normal joint cartilage in individuals without osteoarthritis.”

In 2009, in the Journal, Arthroscopy, Vangsness, Spiker, and Erickson came to a somewhat blasé conclusion, “glucosamine sulfate, glucosamine hydrochloride, and chondroitin sulfate have individually shown inconsistent efficacy in decreasing OA pain and improving joint function.”

The long and the short of it is that these supplements might work. Furthermore, my best guess at this point is that they probably work better for some people than for others. So should you take glucosamine or even chondroitin? All our information at this point says that it is safe to do so. No serious or even moderate side effects have been observed by taking these supplements. Secondly, they might work for some people. How do know if you are one of them? By taking the supplement.

I realize that this post is probably very unsatisfying to many of you, but some are very enthusiastic about glucosamine and chondroitin, and I think that this enthusiasm needs to be tempered by a hard dose of reality.  There is much we simply do not know at this time about the efficacy of these supplements, and more work needs to be done before we can say anything definitive about them.   A recent study shows that large doses of chondroitin (1200 mgs) are effective at reducing symptoms in patients with osteoarthritis of the knee, but given the vagaries of chondroitin absorption (see above), it is unlikely that we can make any hard and fast conclusions about it.

One more note about these supplements.  Several studies have shown that the quality of over-the-counter glucosamine vary considerably.  Be careful what you buy and from whom you buy your supplements.  Consumer Reports has shown that some supplements are even spiked with prescription drugs!  So caveat emptor and do not believe the marketer’s own statements about their supplements.

Induced Pluripotent Stem Cells Make Cartilage


Induced pluripotent stem cells (iPSCs) are made from adult cells through genetic engineering techniques that drive terminally-differentiated adult cells to revert into embryonic-like cells. iPSCs have the capacity to form any cell type in the adult body, and they may represent the future of regenerative medicine when it comes to treatment of some diseases.

On the 30th of October, 2012, scientists from Durham NC reported that they were able to make cartilage from iPSCs. The cartilage made by iPSCs was not simply the fibrous cartilage found in the ribs and between the connection at the pelvis, but the whitish, hyaline cartilage found at weight-bearing joints. Hyaline cartilage acts as a shock absorber at the hip and knee joints and has proven difficult to make in culture.

According the Farshid Guilak, professor of orthopedics surgery at Duke University Medical Center and senior author of this study: “This technique of creating pluripotent stem cells is a way to take adult cells and convert them so that they have the properties of embryonic stem cells.”

Dr. Guilkak continued, “Adult stem cells are limited in what they can do and embryonic stem cells have ethical issues.” What this research shows in a mouse model is that ability to create an unlimited supply of stem cells that can turn into any type of tissue – in this case cartilage, which has no ability to regenerate itself.

Hyaline cartilage, which is found at articular surfaces (the surfaces between joints, allows us to walk and climb stairs. However, the everyday wear-and-tear or an injury can degrade the cartilage, leaving bones to grind against bones. the result is bone fragmentation, extensive inflammation and pain (osteoarthritis), and the replacement of that joint with an artificial joint. Articular cartilage has a very limited ability to repair itself and damage and osteoarthritis are the leading causes of impairment in older people.

Guilak’s research group, led by postdoctoral research fellow, Brian Diekman, is an alternative to other procedures presently in use, which include the application of stem cells from bone marrow or fat to the damaged cartilage.

The main challenge in using iPSCs was differentiate the cells so that they provided a relatively pure population of cartilage-making cells (chondrocytes). To hone their protocol for making and selecting chondrocytes from iPSCs, Diekman devised a technique that caused only those iPSCs that had differentiated into mature chondrocytes to glow a fluorescent green color. This provided a tag that Diekman and his colleagues used to sort the mature chondrocytes from the other cells.

The isolated chondrocytes made beautiful cartilage that had all the strength and resilience of nature cartilage. As noted by Diekman, “This was a multi-step approach, with the initial differentiation, the sorting, and then proceeding to make the tissue (cartilage in this case). What this shows is that iPSCs can be used to make high quality cartilage, either for replacement tissue or as a way to study disease and potential treatments.”

According to Diekman and Guilak, the next step in this research is to use human iPSCS to test and ultimately refine their cartilage-growing protocol. Guilak summarized his work with these words: “The advantage of this technique is that we can grow a continuous supply of cartilage in a dish. In addition to cell-based therapies, iPSC technology can also provide patient-specific cell and tissue models that could be used to screen for drugs to treat osteoarthritis.”

This work was published in the Proceedings of the National Academy of Sciences USA, 2012, DOI: 10.1073/pnas.1210422109.

Creating Cartilage


Cartilage is the shock absorber of the body. It allows two bones to move past each other without deleterious effects. Today, we walk on paved streets and carpeted buildings with stiff floors. Our cartilage takes a constant beating and as we age, it has a tougher and tougher time bouncing back.

As we age, the daily wear and tear eventually grinds this tissue down and movement can become painful and tedious. Osteoarthritis affects over 27 million Americans and it can cause pain, stiff joints, cracking sounds, inflammation and bone spurs.

Cartilage formation depends upon the activity of one cell type – the chondrocyte. With advancing age, chondrocytes divide less and less and eventually, they fall behind making new cartilage to repair the defects generated by everyday wear and tear. In the long-term, chondrocytes can respond to stress by simply dying-off.

Orthopedic specialists consider cartilage regeneration the holy grail of orthopedic medicine. Since people are living longer, orthopedists have taken to cleaning out damaged joints with arthroscopic surgery, braces to stabilize a wobbly gait, and artificial knees and hips to replace heavily damaged joints.

Now, stem cell technology has given the hope of actually re-making new cartilage in aging,arthritic patients. Bio-engineers are working hard to crack the nut of cartilage production. They have identified prominent proteins required to turn stem cells into chrondrocytes, and have also designed three-dimensional scaffolds upon which stem cells will grow and eventually make cartilage. Cartilage-forming cells seem to behave normally if they are constantly surrounded by molecules found in normal cartilage. Also the scaffolding derived from cartilage seems to provide many of the molecular prompts for cartilage behavior.

Much of this is still in the experimental phase, the “stem cell strategy” for re-synthesizing cartilage seems to be one of the best possibilities and clinical trials are in the works in Norway, Spain, Iran, Malaysia, and other places too.

Tissue engineering had its start in the 1970s, and then it comes to cartilage, it has certainly had its ups and downs. For example, the type of cartilage found at the ends of long bones is known as “hyaline cartilage” because of its slippery feel, glassy look, elastic properties and smooth texture. Hyaline cartilage is a terrific weight-bearing cap. Nevertheless attempts to make cartilage at joints has resulted in the production of “fibrocartilage.”

For example, surgeons have often treated arthritic joints by cleaning out bone spurs, scar tissue, and then drilling small holes into the ends of the bones. This causes stem cells to move into the joint and make new cartilage, but they make fibrocartilage instead of hyaline cartilage. Fibrocartilage is found at the place where our pelvic bones join, our intervertebral discs, and our jaw joint. It does not have the ability to resist impact forces the way hyaline cartilage does. Therefore, it erodes quickly at joints. John Sandy, a biochemist at Rush University Medical Center, Chicago put it this way, “Those stem cells that come out are confused. They’re not getting the right signals….So they hit the middle road.” In a study that examined microfracture surgery, two-thirds of athletes who had the procedure showed good results, but only half of those were able to play at their original level for several years.

Chondrocyte transplantation has also been attempted. A Cambridge, MA biotech company called Genzyme has an off-the-shelf product known as Carticel that takes thousands of live chondrocytes from healthy cartilage elsewhere in the body and cultures them to expand their numbers. The expanded chondrocytes are then injected into the affected site. This is known as autologous chondrocyte implantation and this procedure has outperformed microfracture surgery, at least in some studies. Unfortunately, some patients need follow-up surgery, and a nine-year study found that 50% of patients did not improve at all (see Christopher M. Revell, and Kyriacos A. Athanasiou, Success Rates and Immunologic Responses of Autogenic, Allogenic, and Xenogenic Treatments to Repair Articular Cartilage Defects. Tissue Eng Part B Rev. 2009 March; 15(1): 1–15). According to Wan-Ju Li, a tissue engineer at the University of Wisconsin, Madison, chondrocytes lose their ability to form cartilage if they are grown for too many generations in culture.

Can other cells be used to form cartilage? The answer is a clear “yes.” Stem cells from cartilage, tendons, and synovial membranes (the sac that surrounds the joint) can all form cartilage, as can stem cells from fat, and umbilical cord.

The next question is, “how do we coax these stem cells into making cartilage?” What works in culture dishes in the laboratory may not work inside a living joint, but certainly, getting it to work in the laboratory is the first place to start. Several compounds have been found that are definitely pro-cartilage molecules. These include a growth factor called TGF-beta, which jumps starts stems into the cartilage-forming program. However, as John Sandy explains, TGF-beta does not work alone because it will tend to drive cells to form fibrocartilage rather than hyaline cartilage.

The other growth factor needed to turn stem cells into hyaline cartilage-making chondrocytes is fibroblast growth factor-2 (FGF-2; see Andrew M. Handorf and Wan-Ju Li, Fibroblast Growth Factor-2 Primes Human Mesenchymal Stem Cells for Enhanced Chondrogenesis PLoS One 2011; 6(7): e22887). FGF-2 turns on a transcription factor in stem cells called Sox9 which switches on the production of type 2 collagen and aggrecan (two cartilage-specific proteins).

Other booster compounds that increase the cartilage-making profiles of stem cells include a synthetic molecule called kartogenin (Kristen Johnson, et al., A Stem Cell–Based Approach to Cartilage Repair. Science 11 May 2012: Vol. 336 no. 6082 pp. 717-721). Kartogenin inhibits a stem cell protein called filamin A and this unleashes all kinds of cartilage-specific processes in the stem cells. Kartogenin has taken the cartilage camp by storm, and Joan Marini of the National Institutes of Health in Bethesda, MD and Antonella Forlino of the University of Pavia in Italy wrote in the June 28 edition of the New England Journal of Medicine: “Stimulating the differentiation of one’s own stem cells by means of an easily deliverable chemical compound would be more advantageous than using conventional drilling and microfracture techniques.”

Another pro-chondrocyte protein is vimentin, which helps cells assume a round shape. According to Ricky Tuan, tissue engineer at the University of Pittsburg, vimentin pushes bone marrow stem cells into nice round cells that look like chondrocytes. Even more vimentin pushes the cells to make type 2 collagen (cartilage-specific; see Bobick B. E., Tuan R. S., Chen F. H. (2010) The intermediate filament vimentin regulates chondrogenesis of adult human bone marrow-derived multipotent progenitor cells. J. Cell. Biochem 109, 265–276).

Thus with the right blend of compounds, good hyaline cartilage can be made, but according to Ming Pei, an orthopedic surgeon and cell biologist at West Virginia University in Morgantown, making proper hyaline cartilage probably comes down to using the right stem cell. Pei thinks that stem cells from the synovial membrane have an advantage over other stem cells when it comes to cartilage making because of a substance they make.

Pei’s research team mixed the matrix made by synovial stem cells with FGF-2 in a low-oxygen environment. When they added other synovial stem cells those cells ramped up their cartilage making capabilities (Pei M, He F, Kish VL. Expansion on extracellular matrix deposited by human bone marrow stromal cells facilitates stem cell proliferation and tissue-specific lineage potential. Tissue Eng Part A. 2011 Dec;17(23-24):3067-76). These conditions seem to provide a safe place or stem cells to become chondrocytes and make cartilage. Such safe places for stem cells are called “stem cell niches.” Pei’s niche seems to be optimized for stem cells to make cartilage.

In order to get the chondrocytes to make cartilage that sticks together, they need to be in a niche that closely enough resembles their native niche. To mimic this niche, Li and Tuan started to build synthetic scaffolds that they could seed with stem cells. Such matrices definitely improved cartilage production by stem cells. According to Pei, “It’s easy to fabricate and there’s no batch-to-batch difference.”

Li notes that the polymer is designed to degrade after six-twelve months in the body and they have all the strength and mechanical properties to keep the stem cells together until they make a matrix of their own. In 2009, Tuan and Li tested their scaffold by seeding it with human stem cells so that it would create a patch that was inserted into pigs that had suffered cartilage damage. They used two types of cells to seed the matrices – stem cells and mature chondrocytes. After implanting the matrices, those that had been seeded with stem cells make hyaline cartilage, but those seeded with mature chondrocytes made fibrocartilage, after six months. Li reported, “It was glassy cartilage with good mechanical properties.”

As an alternative scaffold, scientists are also using scaffolds made from cartilage procured from cadavers. According to Pei, natural cartilage scaffolds have advantages that synthetic scaffolds do not have, such as chondrocyte-inducing molecules embedded in them.

Other laboratories are using matrices made from fibrin (the stuff blood clots are made from) and seeding with platelets, which are rich in TGF-beta. Doctors at Cairo University in Egypt seeded this scaffold with stem cells that were then implanted into the knees of five patients, all of whom reported improvements after one year.

Regardless of the exact scaffold that is used, Li is buoyantly confident that a stem cell-based strategy will result in making cartilage in the joints of aging patients.

If a treatment is found for osteoarthritis, the next question becomes, “when should the treatment be offered?” David Felson, a rheumatologist at Boston University School of Medicine. notes that knee injuries increase the likelihood a person will suffer from osteoarthritis sixfold. Felson’s research seems to indicate that such injuries “probably account for a great majority of osteoarthritis.”

Early detection is probably not practical, since most people ignore their injuries. Some patients can have bones rubbing together long before they start to experience the pain of osteoarthritis.

However, perhaps chemical markers can help detect the early signs of joint trouble. Carla Scanzello, who works at Rush University Medical Center as a rheumatologist reported that inflammatory molecules that gradually destroy cartilage leave chemical tells that can be detected and might provide a way to detect the early signs of joint damage before symptoms appear (See Carla R. Scanzello, et al., Synovial inflammation in patients undergoing arthroscopic meniscectomy: molecular characterization and relationship with symptoms. Arthritis Rheum. 2011 February; 63(2): 391–400).

Stem cell treatments might also reduce the number of patients who need artificial joint replacements. An artificial hip or knee can last 10-15 years. IF you are older, that is usually not a problem, if you are younger, that becomes a problem. According to Li, there are technical problems to be worked out, but the largest hurdles have been largely conquered, what remains is largely engineering questions. His goal is to eventually make joint replacement a thing of the past and turn orthopedic surgeons into stem cell scientists.